The objective of this research is the development of synthetic methods which will link several protease-resistant proteins to the exterior of a single, central, core enzyme. These multiprotein aggregates should preserve the enzymatic activity of the core enzyme toward low molecular weight substrates, but show greater stability to proteases, lower antigenicity, weaker reactivity toward antibodies to the core protein, and different distribution among tissues than the native core protein. Initial model studies will link avidin molecules to myokinase modified by covalently attached biotin residues, and serum albumin molecules to myokinase modified by covalently attached fatty acid groups. Myokinase will also be bound directly to several lysozyme moieties using a modified active site-directed inhibitor, and to several beta-galactosidase residues by a thiol-specific reagent. Comparison of the properties of these myokinase-protein conjugates with those of native myokinase will establish the feasibility of shielding a core protein from macromolecular recognition using a shield of different proteins. Further studies will modify L-asparaginase, neocarzinostatin, and phenylalanine: ammonia lyase for use in cancer chemotherapy, and enzymes of interest in treatment of enzyme deficiency and storage diseases (glucocer ebrosidase, ceramide trihexoside-alpaa-galactosidase). New reagents for protein modification will be developed to facilitate this work. These studies should increase the utility of therapeutic proteins, by increasing their lifetimes in vivo and decreasing their antigenicity.